IgG、IgM 和 IgG/IgM 自身抗体上 α2,6-唾液酸比率的反向表达与小鼠关节炎和类风湿性关节炎的疾病活动相关。

Reverse expression of α2,6-sialic acid ratios on IgG, IgM, and IgG/IgM autoantibodies correlates with mouse arthritis and rheumatoid arthritis disease activity.

机构信息

Division of Rheumatology, Allergy, and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan, ROC.

Division of Rheumatology, Allergy, and Immunology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.

出版信息

J Chin Med Assoc. 2020 Dec;83(12):1079-1086. doi: 10.1097/JCMA.0000000000000439.

DOI:10.1097/JCMA.0000000000000439

PMID:33009208

Abstract

BACKGROUND

Sialic acids (SIAs), for example, α2,6-SIAs, can link to conserved N-glycans of immunoglobulin G (IgG). In this study, we investigated the correlation between α2,6-SIA on IgG and IgM and the disease activity of arthritis and rheumatoid arthritis (RA) in mice.

METHODS

We measured α2,6-SIA levels in IgGs and IgMs in collagen-induced arthritis (CIA). Additionally, α2,6-SIA levels in rheumatoid factors (RFs) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA patients were measured. Correlations between α2,6-SIA on Igs and CIA were analyzed and also in RA patients by utilizing the disease activity score 28 (DAS28). The ability to differentiate RA progression by Ig and autoantibody α2,6-SIA levels was examined.

RESULTS

In CIA mice, plasma IgG-α2,6-SIA/IgG ratios decreased, whereas plasma IgM-α2,6-SIA/IgM ratios increased. Moreover, arthritis was not observed in collagen-injected mice with decreased IgG-α2,6-SIA/IgG ratios and without increased IgM-α2,6-SIA/IgM ratios. Isolated IgG-α2,6-SIA/IgG ratios displayed a significant inverse correlation with DAS28 scores (r = -0.383, p = 0.037). In contrast, isolated IgM-α2,6-SIA/IgM ratios correlated positively with DAS28 (r = 0.351, p = 0.009). Isolated IgG-anti-CCP-α2,6-SIA/plasma IgG-anti-CCP ratios were differentiated into either the remission (higher ratios) or the nonremission (lower ratios) category (p = 0.061), which is similar to the pattern for C-reactive protein (CRP) (p = 0.041) but different from that for the erythrocyte sedimentation rate (ESR) (p = 0.421). Using multiple linear regression analysis, plasma IgMRF-α2,6-SIA/IgMRF ratios displayed a correlation with DAS28 (p = 0.006), which was also observed in the ESR (p = 0.005), but was different from that for CRP (p = 0.222).

CONCLUSION

Concurrent reverse expression of α2,6-SIA ratios on IgM and IgG correlated with the occurrence of CIA and RA disease activity. Thus, α2,6-SIA ratios on IgG-anti-CCP antibodies and IgMRF are potential markers for evaluating RA disease activities.

摘要

背景

唾液酸（SIAs），例如α2,6-SIAs，可以与免疫球蛋白 G（IgG）上的保守 N-糖结合。在这项研究中，我们研究了 IgG 和 IgM 上的α2,6-SIA 与关节炎和类风湿关节炎（RA）疾病活动之间的相关性。

方法

我们测量了胶原诱导关节炎（CIA）中 IgG 和 IgM 的α2,6-SIA 水平。此外，我们还测量了 RA 患者的类风湿因子（RFs）和抗环瓜氨酸肽（抗-CCP）抗体中的α2,6-SIA 水平。通过利用疾病活动评分 28（DAS28）分析了 Ig 上的α2,6-SIA 与 CIA 之间的相关性，并在 RA 患者中进行了分析。通过 Ig 和自身抗体α2,6-SIA 水平检查了区分 RA 进展的能力。

结果

在 CIA 小鼠中，血浆 IgG-α2,6-SIA/IgG 比值降低，而血浆 IgM-α2,6-SIA/IgM 比值升高。此外，在 IgG-α2,6-SIA/IgG 比值降低且没有 IgM-α2,6-SIA/IgM 比值升高的胶原注射小鼠中未观察到关节炎。分离的 IgG-α2,6-SIA/IgG 比值与 DAS28 评分呈显著负相关（r = -0.383，p = 0.037）。相反，分离的 IgM-α2,6-SIA/IgM 比值与 DAS28 呈正相关（r = 0.351，p = 0.009）。分离的 IgG-抗-CCP-α2,6-SIA/血浆 IgG-抗-CCP 比值分为缓解（比值较高）或未缓解（比值较低）类别（p = 0.061），这与 C 反应蛋白（CRP）（p = 0.041）的模式相似，但与红细胞沉降率（ESR）（p = 0.421）不同。使用多元线性回归分析，血浆 IgM-RF-α2,6-SIA/IgM-RF 比值与 DAS28 相关（p = 0.006），这也与 ESR（p = 0.005）相关，但与 CRP 不同（p = 0.222）。